How does sodium chloride (NaCl) solution contribute to metabolic acidosis?

From the Guidelines

Sodium chloride solution can contribute to acidosis through a process called hyperchloremic metabolic acidosis, and its use should be avoided in large volumes, especially in critically ill patients or those with compromised renal function, due to the risk of worsening acidosis and increasing mortality, as evidenced by the most recent study 1.

Mechanism of Acidosis

When large volumes of normal saline (0.9% sodium chloride) are administered, the relatively high chloride content (154 mEq/L) compared to plasma (approximately 100-110 mEq/L) leads to chloride accumulation in the body. This excess chloride reduces the strong ion difference in plasma, resulting in increased hydrogen ion concentration and decreased pH. Additionally, the kidneys respond to the chloride load by reducing bicarbonate reabsorption, further worsening the acidosis.

Risk Factors

The risk of acidosis from normal saline is higher in patients with compromised renal function who cannot efficiently excrete the excess chloride. To minimize this risk, balanced crystalloid solutions like lactated Ringer's or Plasma-Lyte, which have electrolyte compositions closer to plasma, may be preferred for large-volume fluid replacement. The acidosis from normal saline is typically mild and self-limiting in patients with normal renal function but can be clinically significant in critically ill patients or those receiving large volumes.

Recommendations

Based on the most recent evidence 1, balanced crystalloid solutions are recommended over 0.9% sodium chloride for large-volume fluid replacement in critically ill patients or those with compromised renal function. This recommendation is supported by studies showing reduced incidence of major adverse kidney events and improved acid-base balance with the use of balanced solutions 1. However, it is essential to note that the evidence is not uniform, and some studies have reported no difference in outcomes between balanced and non-balanced crystalloids 1. Nevertheless, the potential benefits of balanced solutions in reducing morbidity and mortality outweigh the risks, and their use is recommended as a precautionary measure.

From the FDA Drug Label

Administration of too much sodium chloride may result in serious electrolyte disturbances with resulting retention of water, edema, loss of potassium and aggravation of an existing acidosis. When intake of sodium chloride is excessive, excretion of crystalloids is increased in an attempt to maintain normal osmotic pressure. Thus there is increased excretion of potassium and of bicarbonate and, consequently, a tendency toward acidosis. Excessive amounts of sodium chloride by any route may cause hypopotassemia and acidosis.

Sodium chloride solution can contribute to acidosis in two ways:

• Aggravation of existing acidosis: Excessive administration of sodium chloride may worsen an existing acidotic state.
• Induction of acidosis: Excessive intake of sodium chloride can lead to increased excretion of bicarbonate, resulting in a tendency toward acidosis, and can also cause hypopotassemia, which may contribute to acidosis 2, 2.

From the Research

Contribution of Sodium Chloride Solution to Acidosis

• Sodium chloride 0.9% solution can cause hyperchloremic metabolic acidosis due to its high chloride concentration compared to plasma 3
• The administration of sodium chloride 0.9% can lead to renal artery vasoconstriction, affecting renal perfusion and contributing to acidosis 3
• Hyperchloremic acidosis is a type of strong-ion acidosis, where the strong-ion difference regulates plasma bicarbonate, with chloride and lactate being the primary strong anions 4
• Dietary sodium chloride intake is independently associated with the degree of hyperchloremic metabolic acidosis in healthy humans consuming a net acid-producing diet 5

Mechanisms and Associations

• The plasma strong-ion difference, including chloride, has a stronger association with plasma bicarbonate than plasma chloride alone 4
• Sodium chloride loads and net acid loads independently predict systemic acid-base status, with increasing degrees of low-grade hyperchloremic metabolic acidosis as the loads increase 5
• The use of sodium bicarbonate for treating metabolic acidosis has been found to increase mortality in children with low chloride levels but decrease mortality in those with high chloride levels 6

Limitations and Considerations

• The sodium-chloride difference is not strongly correlated with base excess in chronic kidney disease, due to the variability of the serum anion gap 7
• A complete blood gas analysis is necessary for the correct diagnosis of acid-base disorders in patients with chronic kidney disease, as the sodium-chloride difference is not an adequate parameter for screening hyperchloremic acidosis 7